1. Field of the Invention
This invention relates generally to the treatment of psychiatric disorders by stimulating appropriate regions of the thalamus, and more particularly to a method of modulating pathological electrical and/or chemical activity of the brain by electrical and/or chemical stimulation of the corresponding nucleus or nuclei of the thalamus, and most specifically to the stimulation of the dorsomedial nucleus of the thalamus.
2. Description of the Prior Art
The treatment of psychiatric disorders by neurosurgical techniques has an extensive history. In the early 1930""s Fulton and Jacobsen first recognized that an experimentally induced neurotic behavior in chimpanzees could be abolished by frontal lobectomy. Within a few years, Freeman and Watts developed the first psychosurgical procedure for humans known as the frontal lobotomy. As the inherent physiology of the frontal lobe became more evident, the original freehand procedure of Freeman and Watts became less and less extensive. By the late 1940""s, the method of stereotaxis, in which the patient""s brain is modeled in 3-dimensional space for exquisite targeting accuracy, merged with lesioning techniques resulting in an even more efficacious and safe psychosurgical procedure. Further developments of stereotactic equipment have combined with novel advancements in functional and anatomic imaging to encompass the state of the art in the neurosurgical treatment of psychiatric disorders today. However, the fundamental limitation of these lesioning techniques is that they are inherently irreversible and static in nature. There is no proverbial xe2x80x9coffxe2x80x9d switch to alleviate side effects and no way to adjust the desirable effects in response to a patient""s changing symptom profile.
Within the field of neurosurgery, the use of electrical stimulation for treating pathologies, including such disorders as compulsive eating, chronic pain, and movement disorders, such as Parkinson""s disease essential tremor, has been widely discussed in the literature. It has been recognized that electrical stimulation holds significant advantages over alternative methods of treatment, for example lesioning, inasmuch as lesioning can only destroy nerve activity. In many instances, the preferred effect is to stimulate or reversibly block nervous tissue. Electrical stimulation permits such stimulation of the target neural structures, and equally importantly, it does not require the destruction of the nervous tissue (it is a reversible process, which can literally be shut off or removed at will).
Another technique which offers the ability to affect neuronal function in a reversible and dynamic fashion is the delivery of drugs directly to target tissues via a subcutaneously implanted pump. Such drugs, either traditional psychiatric agents or chemicals mimicking neurotransmitters, could be instilled at such low doses as to completely avoid the side effects so common to moden pharmacotherapy. Such doses could also be tailored in magnitutde with regard to a particular patient""s varying symptomatology. A chemical neuromodulating system could be implanted as a primary treatment strategy or in combination with an electrically based one. A combination therapeutic approach, one combining electrical and chemical means, would be penultimate to regenerating healthy neuronal tissue.
Within this field, however, disorders manifesting gross physical dysfunction, not otherwise determinable as having emotional or psychiatric origins, comprise the vast majority of those pathologies treated by deep brain stimulation. A noteworthy example of treatment of a gross physical disorder by electrical stimulation is included in the work of Alim Benabid, and his research team, who have proposed a method of reducing, and in some cases eliminating, the temor associated with Parkinson""s disease by the application of a high frequency electrical pulse directly to the subthalamic nucleus (see Neurosurgical Operative Atlas, Vol. 8, March 1999, pp. 195-207, Chronic Subthalamic Nucleus Stimulation For Parkinson""s Disease; and New England Journal of Medicine, Vol. 339, October 1998, pp. 105-1111, Electrical Stimulation of the Subthalamic Nucleus in Advanced Parkinson""s Disease).
Conversely, direct neuroaugmentation treatments for disorders which have traditionally been treated by behavioral therapy or psychiatric drugs, has been largely limited to the stereotactic lesioning procedures mentioned above. The are four lesioning techniques mostly in use today: cingulotomy, capsulotomy, subcaudate tractotomy, and limbic leucotomy. Such procedures have been applied to date in the treatment of Affective disorders and Anxiety disorders. If one critically examines the results of these procedures in the literature, it would be apparent, when applied to a carefully selected patient population in conjuction with modern equipment and imaging techniques, these procedures are both efficacious and safe. In fact, in a certain subset of patients who have failed all conventional (pharmacotherapy and psychotherapy) treatments, these neurosurgical procedures are the only efficacious options available. If would follow that electrical and/or chemical neuromodulating techniques with their inherent reversibility and adjustability would an even better solution than the traditional lesioning techniques. To date, however, intracranial neuromodulation techniques have been largely unexplored. Only recently, in the Oct. 30, 1999 issue of Lancet, have Meyerson et al. described a technique for deep brain electrical stimulation of the anterior internal capsule for OCD patients. While the results are preliminary, they are also quite promising as three of the four patients had good results.
Another effort has been made to treat psychiatric disorders via peripheral nerve stimulation. A noteworthy example is the effort to control compulsive eating disorders by stimulation of the vagus nerve which has been described by Wernicke, et al. in U.S. Pat. No. 5,263,480. This treatment seeks to induce a satiety effect by stimulating the afferent vagal fibers of the stomach. For patients having weak emotional and/or psychological components to their eating disorders, this treament can be effective insofar as it eliminates the additional (quasi-normal) physio-chemical stimulus to continue eating. This is especially true for patients who exhibit subnormal independent functioning of these fibers of the vagus nerve. For compulsive eating patients who are not suffering from an insufficient level of afferent vagal nerve activity resulting from sufficient food intake, however, the over stimulation of the vagus nerve and potential resultant over abundance of satiety mediating chemicals (cholecystokinin and pancreatic glucagon) may have little effect It has even been suggested that continued compulsive eating, despite overstimulation of the vagus nerve, may exacerbate the emotional component of the patient""s disorder. This, therefore, begs the question, is vagus nerve stimulation useful in treating the psychological component of the disorder of compulsive eating, or is it simply a method of minimizing the additional, but natural, pressures to eat because of normal physical hunger. More generally, the question may be asked, is peripheral nerve stimulation of any kind the most appropriate method of treatment for disorders which are, at the core, the result of a pathology exhibited in the brain.
If the answer to this question is that the stimulation of a peripheral nerve can result in the release of a chemical which specifically counteracts the psychological pathology, for example if the release of greater amounts of cholecystokinin and pancreatic glucagon had a direct effect on the pathology exhibited in the brain, then, for that patient, the treatment will have a greater probability of success. If, however, as is most probably the case, the increase in the level of activity of the peripheral nerve does not result in the release of such a chemical, and therefore, has no effect on the area of the brain responsible for the emotional/psychiatric component of the disorder, then the treatment will have a much lower probability of success.
The impetus, therefore, would be to treat psychiatric disorders with direct modulation of activity in that portion of the brain causing the pathological behavior Unfortunately, the ability to determine what region of the brain is responsible for a given patient""s disorder is very difficult, and even more importantly, does not usually provide consistent patterns across a population of similarly afflicted patients. By this it is meant that the region of the brain which causes the behavioral pathology of one compulsively eating patient, for example, does not necessarily correspond in any way with the region of another compulsively eating patient.
In some manner, however, the determination of what regions of the brain are exhibiting pathological function must be determined. Fortunately, a method for determining precisely this has been developed by a number of researchers. Normal brain function can be characterized by four discrete frequencies of electrical output. Other frequencies are almost exclusively associated with pathology. The use of magnetoencephalography (MEG scans) has permitted quantificaion of electrical activity in specific regions of the brain. It has been proposed that MEG scans may be used to identify regions exhibiting pathological electrical activity. The resolution of the MEG scans of the brain are highly accurate (sub-one millimeter accuracy), however, correlating the MEG scan with MRI images for the surgical purposes of identifying anatomical structures limits the overall resolution for surgical purposes to a volume of 10 to 30 cubic millimeters. As stated above, however, simply identifying the regions of the brain which are exhibiting pathological electrical activity for a specific patient is not sufficient to generalize across a large population of patients, even if they are exhibiting identical disorders.
Fortunately, the architecture of the brain provides a substantial advantage in the search for a generic solution. This design advantage takes the form of a centralized signalling nexus through which many of the brain""s disparate functions are channeled in an organized and predictable manner. More particularly, the thalamus is comprised of a large plurality (as many as one hundred, or more) of nerve bundles, or nuclei, which receives and channels nerve activity from all areas of the nervous system and interconnects various activities within the brain. The thalamus has been metaphorically described by some as the brain""s equivalent of a highly organized train station. Many different train tracks come together, and many trains carrying many different cargos enter, however, if one has a schedule and a map, it is easy to find all the trains which carry coal (whether from Pennsylvania, West Virginia, Tennessee, or Arkansas), because all coal carriers are routed through the same tracks. It is this key which permits the treatment of common psychiatric disorders by brain stimulation of one specific area, rather than having to customize the (gross) placement of the stimulator and/or catheter for each patient.
It is therefore the principal object of the present invention to provide a more generically applicable method for treating certain psychiatric disorders.
It is further an object of the present invention to provide a fully reversible and adjustable method of treating certain psychiatric disorders.
It is still further an object of the present invention to provide a method of treating certain psychiatric disorders the effectiveness of which may be evaluated rapidly.
It is also an object of the present invention to provide a method of interventionally treating certain psychiatric disorders while minimizing the necessary pathological investigation.
The preceding objects are provided in the present invention, which comprises new and novel methods of treating psychiatric disorders by implantation of stimulation lectrodes and/or drug-delivery catheters at a specific location in the thalamus. In another aspect, the present invention also comprises new and novel methods for identifying the proper positioning of the electrodes and/or catheters within the thalamus for a given specific psychiatric disorder. More particularly, in the first aspect, the present invention comprises a method of therapeutically treating a psychiatric disorder by surgically implanting an electrode and/or drug-delivery catheter into a predetermined site within the brain of the patient, wherein the predetermined site is selected from within the dorsomedial thalamus. Referring more particularly to FIG. 1, the dorsomedial nucleus 101 is located dorsal to the medial thalamic nucleus 102 and medial to the, intralaminal nucleii 103. The dorsomedial thalamic nucleus is coupled most directly to the orbitofrontal cerebral cortex which is most associated with personality and behavior. The OFC is particularly implicated in the pathogenesis of various psychiatric diseases. There are two main loops connecting the dorsomedial nucleus and the OFC. A direct, reciprocally excitatory loop is mediated by the neurotransmitter glutamate. An indirect, modulatory loop occurs via connections through the ventromedial striatum and glocus pallidus, and is thought to be mediated by multiple neurotransmitters including: GABA, dopamine, and serotonin. The dorsomedial nucleus also has connections to the limbic system. The limibc system is a group of structures in the brain which are thought to mediate the emotional state. At the core of this system is the Papez circuit, first illustrated in 1937, which includes the cingulate gyrus, the anterior thalamic nucleus, the amygdala, the fornix, and the mamillary bodies. The dorsomedial thalamic nucleus has been shown to have connections with the basolateral amygdala.
In the first aspect of the invention, therefore, the proximal end of the electrode and/or catheter is coupled to an electrical signal source and/or drug delivery pump which, in turn, is operated to stimulate the predetermined treatment site in the orbitofrontal cortex of the brain, such that the clinical effects of the psychiatric disorder are reduced.
In the second aspect, the present invention comprises a method of determining the proper therapeutic treatment, i.e., the proper position or placement of the electrodes, for a specific psychological disorder comprising the steps of identifying a large sampling of patients, each exhibiting a common specific psychological disorder and then identifying which common region or nuclei of their thalamuses exhibits pathological electrical activity during manifestations of the specific psychological disorder. The common regions demonstrating this pathological activity constitute the predetermined treatment site, whereafter a suitable means for affecting the activity of said predetermined treatment site may be employed to ameliorate the psychological disorder generically with a high probability of success.
In particular, the region identified above, the dorsomedial thalamic nucleus is herein identified by its known anatomical connections and functional brain imaging as being actively involved in channeling or gating the pathological electrical and/or metabolic activity associated with psychiatric disorders. It is important to note that this region, its functions, and its connections are common structural features of human brains, and therefore is a common target across a large number of patients. As suggested above, this commonality of function and structure within the thalamus allows for common treatment targeting, even in instances wherein different patients have other disparate locations within their brains that also exhibit pathological electrical and/or metabolic activity.